US20120022338A1 - Apparatus, systems, methods and computer-accessible medium for analyzing information regarding cardiovascular diseases and functions - Google Patents

Apparatus, systems, methods and computer-accessible medium for analyzing information regarding cardiovascular diseases and functions Download PDF

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US20120022338A1
US20120022338A1 US13/118,109 US201113118109A US2012022338A1 US 20120022338 A1 US20120022338 A1 US 20120022338A1 US 201113118109 A US201113118109 A US 201113118109A US 2012022338 A1 US2012022338 A1 US 2012022338A1
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Prior art keywords
arrangement
tissue
characteristic
heart
blood
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Balachundhar Subramaniam
II William C. Warger
Brett Simon
Guillermo J. Tearney
Li Li
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General Hospital Corp
Beth Israel Deaconess Medical Center Inc
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General Hospital Corp
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Assigned to THE GENERAL HOSPITAL CORPORATION reassignment THE GENERAL HOSPITAL CORPORATION ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: LI, LI, TEARNEY, GUILLERMO J., WARGER, WILLIAM C., II
Assigned to BETH ISRAEL DEACONESS MEDICAL CENTER, INC. reassignment BETH ISRAEL DEACONESS MEDICAL CENTER, INC. ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: SIMON, BRETT, SUBRAMANIAM, BALACHUNDHAR
Publication of US20120022338A1 publication Critical patent/US20120022338A1/en
Priority to US14/627,226 priority patent/US20150223698A1/en
Priority to US17/690,637 priority patent/US20220192503A1/en
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0093—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy
    • A61B5/0095—Detecting, measuring or recording by applying one single type of energy and measuring its conversion into another type of energy by applying light and detecting acoustic waves, i.e. photoacoustic measurements
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    • A61B5/026—Measuring blood flow
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    • A61B5/14535—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue for measuring haematocrit
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    • A61B5/1455—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters
    • A61B5/14551—Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissue using optical sensors, e.g. spectral photometrical oximeters for measuring blood gases
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    • A61B5/0033—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room
    • A61B5/004—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part
    • A61B5/0044—Features or image-related aspects of imaging apparatus classified in A61B5/00, e.g. for MRI, optical tomography or impedance tomography apparatus; arrangements of imaging apparatus in a room adapted for image acquisition of a particular organ or body part for the heart
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    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0073—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by tomography, i.e. reconstruction of 3D images from 2D projections

Definitions

  • Exemplary embodiments of the present disclosure relates generally to apparatus, systems, methods and computer accessible medium for analyzing information regarding cardiovascular diseases and functions, and more particular apparatus, systems, methods and computer accessible medium analyzing for at least one characteristic of an anatomical structure, and even more particularly to the utilization of at least one electromagnetic or acoustic wave to diagnose cardiovascular diseases and/or measure cardiac functions.
  • a coronary artery disease mainly caused by atherosclerosis
  • atherosclerosis is the leading cause of death worldwide.
  • Such disease occurs when fats, lipid, calcium, collagen, macrophage and other substances form a plaque on the walls of a artery.
  • vulnerable plaques There may exist a group of “vulnerable plaques” that can be characterized by the anatomy and composition. These vulnerable plaques tend to rupture, which can cause either a myocardial infarction or a stroke, and can ultimately lead to death.
  • Computed tomography (“CT”) and magnetic resonance imaging (“MRI”) have been described as non-invasive alternatives for diagnosing coronary artery diseases. These techniques are capable of imaging the bulk structure of the coronary artery wall, but are relatively expensive, use contrast administration, which are features that may not be ideal for screening large populations for coronary artery disease and vulnerable plaque.
  • mixed venous oxygen saturation blood oxygenation measured from the pulmonary artery
  • Mixed venous oxygen saturation less than 65% has been associated with poor surgical outcomes (see, e.g., Jhanji, S., et al. “Microvascular flow and tissue oxygenation after major abdominal surgery: association with post-operative complications”, Intensive Care Medicine 35, 671-677 (2009)), with a majority of these complications occurring during a low cardiorespiratory reserve, where pulse oximetry is ineffective.
  • a continuous display of a mixed venous oxygen saturation can be possible with oximetric Swan Ganz catheters, inserted transcutaneously through the jugular vein into the pulmonary artery. These catheters are generally invasive, -and can cause substantial added morbidity and mortality to critically ill patients. As a result, continuous monitoring of cardiac functions, such as blood oxygenation in a major blood vessel attached to the heart in acute patients, can be a significant challenge, especially for those with low blood volume following trauma (e.g., traffic accidents or combat situations), shock (e.g., sepsis, hypovolemia or cardiogenic) and burns.
  • trauma e.g., traffic accidents or combat situations
  • shock e.g., sepsis, hypovolemia or cardiogenic
  • Pulse oximetry procedures can measure oxygen saturation from the peripheral arteries, such as fingers and earlobes, and can provide an approximate quantity of oxygen supplied to the organs.
  • This procedure has been beneficially used for a clinical care of patients in emergency rooms, medical and surgical floors, operating rooms, and intensive care units, as it assist with the detection of patients prone to hypoxic events.
  • This technique relies on a consistent perfusion of all peripheral arteries, and the inaccuracy likely increases with a decreased oxygen saturation.
  • Another object of another exemplary embodiment of the present disclosure is to provide apparatus, systems, methods and computer accessible medium for diagnosing cardiovascular disease and vulnerable plaque.
  • Another object of another exemplary embodiment of the present disclosure can be to provide apparatus, systems, methods and computer accessible medium for measuring cardiac functions during most or all key physiologic states.
  • a first (e.g., excitation) radiation can be used to illuminate a tissue
  • a second (e.g., emission) radiation can be generate as a result of an interaction between the tissue and the first radiation.
  • the second radiation can be measured, a measurement as a dataset can be made, and the dataset can be analyzed to determine at least one characteristic of the tissue.
  • a source for providing the excitation radiation and/or a detector to measure the emission radiation can be placed outside the tissue.
  • the radiation can be an electromagnetic wave and/or an acoustic wave.
  • the tissue can be a part of a heart, including, e.g., a left or a right ventricle, a left or right atrium, a myocardium, a mitral valve, a tricuspid valve, an aortic valve, a pulmonary valve, a pericardium, or a pericardial fluid, etc.
  • the tissue can also be a blood vessel attached to a heart, including, e.g., an aorta, a pulmonary artery, a pulmonary vein, an inferior vena cava, a superior vena cava, a coronary artery, and/or a coronary vein, etc.
  • the tissue can further be blood in a blood vessel, and/or an atherosclerotic plaque in a blood vessel or a heart.
  • the measurable characteristic of the tissue can include, but is not limited to, an anatomy or composition of an atherosclerotic plaque, or an oxygen saturation level of a blood, etc.
  • apparatus and method can be provided for determining information regarding a tissue or an object at or within the tissue. For example, with at least one first arrangement which is situated inside a particular organ of the body, it is possible to generate at least one electromagnetic radiation in the tissue, wherein the tissue is different from and outside of the particular organ.
  • the particular signals that are responsive to the at least one electromagnetic radiation can be detected (e.g., possibly with at least one second arrangement), at least one characteristic of the tissue and/or information regarding the object at or in the tissue can be determined (e.g., with the second arrangement(s)).
  • the tissue can be different from and outside of the particular organ, and the first arrangement(s) can be situated inside a particular organ of the body.
  • the tissue can be different from and outside of the particular organ, and the first arrangement(s) can be situated inside a particular organ of the body.
  • the characteristic(s) can include (i) blood, (ii) one or more major blood vessels coupled to a heart, and/or (iii) one or more portions of the heart.
  • the particular organ can be an esophagus.
  • the second arrangement(s) can be further configured to determine further information to identify at least a possibility at least one coronary artery disease.
  • the first and/or second arrangement(s) can be structured and sized to be at least partially situated within the esophagus.
  • the first and/or second arrangement can be (i) photoacoustic arrangement, (ii) a fluorescence arrangement, (iii) an optical spectroscopy arrangement, (iv) a laser speckle imaging arrangement, (v) an optical tomography arrangement, and/or (vi) an ultrasound arrangement.
  • the first and/or second arrangement(s) can be included with or in a transnasal device.
  • At least one third arrangement can be provided which is configured to generate at least one image of the tissue as a function of the information.
  • the third arrangement(s) can be configured to obtain data for (i) a structure of the tissue, and (ii) the characteristic(s) approximately simultaneously.
  • the data can include at least one image of (i) the structure of the tissue, and/or (ii) the characteristic(s) superimposed on one another.
  • the second arrangement(s) can further measure at least one characteristic of at least one further tissue which includes one or more other tissues in addition to the one or more major blood vessel or portion of the heart.
  • At least one fourth arrangement can also be provided which is configured to generate at least one image of the tissue and a further tissue that is in a proximity of the tissue.
  • Such fourth arrangement(s) can include an ultrasound arrangement.
  • apparatus and method can be provided for determining at least one characteristic of an anatomical structure. For example, with at least one first photo-acoustic arrangement, a generation of an acoustic wave can be caused in the anatomical structure. The acoustic wave can be detected, and (possibly with at least one second arrangement), at least one characteristic of blood can be measured within the anatomical structure which is (i) one or more of major blood vessels coupled to a heart, and/or (ii) one or more portions of the heart. The measurement can be performed outside of the anatomical structure.
  • the first arrangement(s) and/or the second arrangement(s) can be structured and sized to be at least partially situated within an esophagus.
  • the characteristic(s) of the anatomical structure can include an oxygen saturation, a cardiac output, a blood flow, a total blood content and/or a blood hematocrit.
  • the oxygen saturation characteristic(s) can include a venous oxygen saturation and/or a arterial oxygen saturation.
  • the first arrangement(s) and/or the second arrangement(s) can be included with a transnasal device. Further, it is possible to generate at least one image of the anatomical structure as a function of the acoustic wave, e.g., using at least one third arrangement.
  • Such exemplary data can include at least one image of: (i) the structure of the anatomical structure, and/or (ii) the characteristic(s) of the anatomical structure superimposed on one another.
  • FIG. 1 is a diagram of a wireless transesophageal pill endoscope arrangement/apparatus according an exemplary embodiment of the present disclosure, which can access the cardiovascular diseases and functions;
  • FIG. 2( a ) is a diagram of the transesophageal pill endoscope on a string according another exemplary embodiment of the present disclosure, which can access the cardiovascular diseases and functions;
  • FIG. 2( b ) is a diagram of the transesophageal pill endoscope on a steering string according still another exemplary embodiment of the present disclosure
  • FIG. 3( a ) is a diagram of an apparatus according an exemplary embodiment of the present disclosure which includes an inflatable balloon;
  • FIG. 3( b ) is a diagram of the apparatus according an exemplary embodiment of the present disclosure which includes a guide wire;
  • FIG. 4( a ) is an illustration of an exemplary method which introduce the apparatus (including the pill) according an exemplary embodiment of the present disclosure into a subject;
  • FIG. 4( b ) is an illustration of an exemplary method which introduce the apparatus (including the transnasal pill) according another exemplary embodiment of the present disclosure into a subject;
  • FIG. 4( b ) is an illustration of an exemplary method which introduce the apparatus (including the transnasal tube) according still another exemplary embodiment of the present disclosure into a subject;
  • FIG. 5( a ) is an illustration of an exemplary configuration of the apparatus according a further exemplary embodiment of the present disclosure, where an exemplary transesophageal pill endoscope can provide an excitation radiation, and an emission radiation can be detected by a detector placed outside of a subject;
  • FIG. 5( b ) is an illustration of an exemplary configuration of the apparatus according yet another exemplary embodiment of the present disclosure, where a source outside of a subject provides an excitation radiation, and an emission radiation can be detected by the exemplary transesophageal pill endoscope;
  • FIG. 5( c ) is an illustration of an exemplary configuration of the apparatus according still further exemplary embodiment of the present disclosure, where a source outside of the subject provides an excitation radiation, and an emission radiation can be detected by an exemplary detector placed outside of a subject;
  • FIG. 5( d ) is an illustration of a configuration of another apparatus according to according an exemplary embodiment of the present disclosure, where the transesophageal pill endoscope provides an excitation radiation, and an emission radiation can be detected by the exemplary detector located inside a heart and/or a blood vessel;
  • FIG. 5( e ) is an illustration of a configuration of a further apparatus according to according an exemplary embodiment of the present disclosure, where a source located inside a heart or a blood vessel provides an excitation radiation, and an emission radiation can be detected by the transesophageal pill endoscope;
  • FIG. 6( a )- 6 ( g ) are exemplary illustration of an exemplary configuration of still another apparatus according a further exemplary embodiment of the present disclosure, which is configured to have a photoacoustic set-up configuration;
  • FIG. 7 is an illustration of an exemplary configuration of a further apparatus according a still further exemplary embodiment of the present disclosure, which is configured to have a fluorescence imaging set-up configuration;
  • FIG. 8 is an exemplary configuration of a further apparatus according yet another exemplary embodiment of the present disclosure, which is configured to have an optical spectroscopy set-up configuration, with associated plots provided in the illustration;
  • FIG. 9 is an exemplary configuration of another apparatus according still another exemplary embodiment of the present disclosure, which is configured to have a laser speckle imaging set-up configuration, with associated plots provided in the illustration;
  • FIG. 10 is an exemplary configuration of a further apparatus according yet another exemplary embodiment of the present disclosure, which is configured to have an optical tomography set-up configuration;
  • FIG. 11 is an exemplary configuration of a still further apparatus according a further exemplary embodiment of the present disclosure, which is configured to have an ultrasound imaging set-up configuration.
  • a pill endoscope 101 sized to fit inside an esophagus, can be provided, which can comprise a biocompatible housing 102 , a power unit 103 (e.g., a battery), a source 104 (e.g., an electro-magnetic radiation source) that can provide a first radiation 105 to excite a tissue, a detector 106 that can transfer a second radiation 107 emitted from the tissue to a first signal (e.g., an electric voltage), a transmitter 108 (e.g., a radio-frequency transmitter) that can convert the first signal into a second signal 109 (e.g., a radio-frequency electromagnetic wave).
  • a power unit 103 e.g., a battery
  • a source 104 e.g., an electro-magnetic radiation source
  • a detector 106 that can transfer a second radiation 107 emitted from the tissue to a first signal (e.g., an electric voltage)
  • a transmitter 108 e.g
  • the second signal 109 can be acquired by a receiver 110 (e.g., an antenna), stored as a dataset on a memory 111 or in another storage device (e.g., RAM, ROM, hard drive, etc.), and analyzed by one or more computers 112 to provide at least one characteristic of the tissue.
  • a receiver 110 e.g., an antenna
  • a memory 111 e.g., RAM, ROM, hard drive, etc.
  • the pill endoscope 101 can further include a sensor to measure a motion of an esophageal tissue, a temperature, a PH value and/or a pressure, etc. These exemplary measurements can be used to determine the current position of the pill endoscope 101 with and/or without operator intervention.
  • the pill endoscope 101 can be carried by peristalsis through a digestive tract, and can also move independently from peristalsis via exemplary components for a magnetic steering, active propelling and/or robotic movement.
  • the receiver 110 and the memory/storage device 111 can be made into a portable device, and carried by a subject during data acquisition. Alternatively or in addition, the pill endoscope 101 can have an onboard memory/storage to store the dataset; thus making the transmitter 108 unnecessary.
  • the pill endoscope 101 can also include components providing facilitating an intervention, such as biopsy, treatment, etc. The measured characteristics of the tissue can further be used to guide the intervention by providing localization information and/or assisting in a selection of a personalized treatment.
  • a transesophageal pill endoscope 201 of this exemplary embodiment can include a string 202 .
  • the string 202 can comprise a wire 204 that can deliver power and/or a first radiation to an excitation source 203 , and/or a second wire 206 that can provide a signal generated by an emission detector 205 to an external receiver.
  • FIG. 2( a ) Another exemplary embodiment of the method and apparatus according to a further exemplary embodiment of the present disclosure is illustrated in FIG. 2( a ).
  • a transesophageal pill endoscope 201 of this exemplary embodiment can include a string 202 .
  • the string 202 can comprise a wire 204 that can deliver power and/or a first radiation to an excitation source 203 , and/or a second wire 206 that can provide a signal generated by an emission detector 205 to an external receiver.
  • FIG. 2( b ) shows a detailed illustration of the transesophageal pill endoscope 201 in which the string 202 can further be used to steer the pill endoscope 201 through translation 221 , rotation 222 and/or flex 223 , e.g., by using controls placed on the proximal end.
  • the pill endoscope 201 can also be retrieved by pulling the string 202 .
  • a transesophageal pill endoscope 310 can also include an inflatable balloon 311 .
  • the balloon 311 can be inflated (e.g., by providing an inflation medium via an inflation arrangement) to anchor the pill endoscope 310 in position, thus facilitating a continuous measurement of the tissue for a prolonged time period.
  • the inflating medium can include air, water, deuterized water, saline, etc.
  • an inflating medium e.g., water
  • an inflating medium can further provide a proper acoustic coupling between the detector and the esophageal wall to minimize signal loss.
  • FIG. 3( b ) shows another transesophageal pill endoscope 320 according to a further exemplary embodiment of the present disclosure that can operate with a guide wire 321 .
  • the pill endoscope 320 can have an attachment 322 that can hook itself to the guide wire 321 .
  • An introduction of the pill endoscope 320 using the guide wire 321 can avoid unwanted rolling.
  • the guide wire 321 can further include a stopper 323 , which can stop the pill endoscope 320 at one or more particular locations to measure a tissue of interest.
  • FIGS. 4( a ) and 4 ( b ) illustrates two possible ways, respectively, to introduce the pill endoscope into an esophagus.
  • FIG. 4 a shows a transesophageal pill endoscope 401 according yet another exemplary embodiment of the present disclosure that can be introduced through the mouth, and swallowed into the esophagus.
  • FIG. 4( b ) illustrates another transesophageal pill endoscope 411 according still another exemplary embodiment of the present disclosure that can be introduced alternatively through a nasal orifice via a nasopharynx into the esophagus.
  • the trans-nasal introduction can be useful for placing the pill endoscope 411 with a string.
  • such introduction of the pill endoscope 411 is performed via a relatively smaller diameter, it can be tolerated better by awake or mildly sedated subjects, and is can be suitable for continuous assessment of cardiac functions of a subject in an intensive care unit.
  • the transnasal device can include a catheter or tube 421 that can be similarly inserted through the nose, until the electromagnetic radiation transducing arrangement/apparatus 422 is located in the esophagus, e.g., adjacent to the heart.
  • the tube can include a balloon that surrounds such portion of the device.
  • a pressure transducer 423 can be placed near the distal end of the device to provide pressure measurements that can assist in the automatic placement of the active portion of the device within the esophagus, such that it is located near the cardiac structures of interest.
  • FIG. 5( a ) shows another arrangement according to still another exemplary embodiment of the present disclosure, where a source 501 inside an esophagus can generate an excitation radiation 502 to illuminate the tissue, and an emission radiation 504 from the tissue can be detected by a detector 504 placed outside of the subject (e.g., on the thorax).
  • a source 501 inside an esophagus can generate an excitation radiation 502 to illuminate the tissue
  • an emission radiation 504 from the tissue can be detected by a detector 504 placed outside of the subject (e.g., on the thorax).
  • FIG. 5( a ) shows another arrangement according to still another exemplary embodiment of the present disclosure, where a source 501 inside an esophagus can generate an excitation radiation 502 to illuminate the tissue, and an emission radiation 504 from the tissue can be detected by a detector 504 placed outside of the subject (e.g., on the thorax).
  • a detector 504 placed outside of the subject (e.g
  • FIG. 5( b ) shows yet another arrangement according to a further exemplary embodiment of the present disclosure, where a source 511 placed outside of a subject can emit an excitation radiation 512 , and a detector 513 inside an esophagus can detect an emission radiation 514 .
  • FIG. 5( c ) shows another arrangement according to a still further exemplary embodiment of the present disclosure, where both a source 521 and a detector 523 are placed outside of the subject.
  • FIG. 5( d ) illustrates another arrangement according to yet another exemplary embodiment of the present disclosure, where a source 531 inside an esophagus can provide an excitation radiation 532 , and a detector 533 inside a blood vessel or a part of a heart can measure an emission radiation 534 .
  • FIG. 5( d ) illustrates another arrangement according to yet another exemplary embodiment of the present disclosure, where a source 531 inside an esophagus can provide an excitation radiation 532 , and a detector 533 inside a blood vessel or a part of a heart can measure an emission radiation 534 .
  • FIG. 5( e ) shows a further arrangement according to a further exemplary embodiment of the present disclosure, where a source 541 is placed in a heart or a blood vessel can provide an excitation radiation 542 , and a detector 543 in an esophagus can measure an emission radiation 544 .
  • the exemplary arrangement/apparatus can include a photoacoustic arrangement.
  • a photoacoustic arrangement can be used to illuminate the tissue using an electromagnetic wave and/or radiation that can vary in intensity as a function of time, and this arrangement can detect an acoustic wave (e.g., a photoacoustic wave) provided from the tissue through a thermoelastic coupling process/procedure after absorbing one or more portions of the electromagnetic energy.
  • the resultant acoustic wave can be propagated through the tissue with an attenuation and scattering that is weaker than that of a light.
  • the exemplary photoacoustic device/arrangement can be used to interrogate the tissue at a great depth (on the order of centimeters) with a high resolution (e.g., ⁇ 1 mm).
  • amplitude and/or a temporal profile of the detected ultrasound wave can provide the location, shape and/or quantity of the absorbing tissue.
  • lipid a major constituent of atherosclerotic plaques
  • the exemplary photoacoustic device with the near-infrared optical excitation (e.g., 900-1800 nm) to detect plaque
  • hemoglobin in blood can be detected using light with visible to near-infrared wavelength (e.g., 500-1100 nm) to depict the lumen of a heart or a blood vessel.
  • it can be preferable to detect lipid, or more specifically, cholesterol or cholesterol esters, within the coronary artery wall.
  • cholesterol absorption peaks including those, e.g., around 950 nm, 1205 nm, 1750 nm, can be targeted by the incident optical radiation to create absorption or photo-acoustic effects that can be detected by the exemplary arrangements according to certain exemplary embodiments of the present disclosure. In so doing, it is possible (e.g., using such exemplary arrangements) to provide a screening diagnosis of the presence or absence of vulnerable plaque.
  • an injectable exogenous chromogenic contrast agent e.g., indocyanine green
  • an injectable exogenous chromogenic contrast agent can be used to tag a tissue of interest, or may be preferentially localized by enhanced uptake and/or retention, allowing a characteristic of the tagged tissue, such as leaky vessels known to be common in the lipid core of vulnerable plaque, be obtained using excitation wavelength close to the absorption peak of the contrast agent (e.g., approximately 800 nm for indocyanine green).
  • Exemplary photoacoustic methods can be used for quantifying the optical, thermal, and mechanical properties of a tissue. According to the difference in one or several measurable properties, the spatial and/or temporal distribution of different tissue constituents can be obtained. For example, because the oxy-hemoglobin and deoxy-hemoglobin have distinct optical absorption spectra, a plurality of photo-acoustic signals from blood can be acquired using optical excitation at a plurality of excitation wavelengths, Then, the local concentrations of the oxy-hemoglobin (C HbO ) and deoxy-hemoglobin (C HbR ) can be calculated from these photo-acoustic measurements.
  • C HbO oxy-hemoglobin
  • C HbR deoxy-hemoglobin
  • a blood oxygen saturation level C HbO /(C HbO +C HbR )
  • the total hemoglobin concentration C HbO +C HbR
  • the blood hematocrit In contrast to the traditional pulse oximetry, photoacoustic measurement of blood oxygenation works in patients with/without pulsation and maintains consistent accuracy when measuring deoxygenated and oxygenated blood.
  • the exemplary photo-acoustic measurements made using excitation at a plurality of visible for near-infrared spectral bands can be used to quantify the distribution of lipid, calcium and collagen in a blood vessel wall, to detect or characterize an atherosclerotic plaque.
  • a photoacoustic device can further sense temperature in tissue to assess the macrophage activity in an atherosclerotic plaque, because the photo-acoustic amplitude increases as temperature increases.
  • the velocity of the blood can also be measured by a photo-acoustic set-up using the Doppler principle.
  • photoacoustic method can facilitate an assessment of to which extent a stenosis impedes oxygen delivery to the heart, by measuring the blood flow and oxygenation at different locations of the blood vessel. Since the dimension of a blood vessel, oxygenation and flow can be measured using photoacoustic methods, a photo-acoustic embodiment of the present disclosure can further measure a cardiac output, a cardiac index, the pulmonary oxygen uptake, oxygen delivery to different parts of a body, etc.
  • FIG. 6( a ) shows one exemplary photoacoustic arrangement according to another exemplary embodiment of the present disclosure, which is provided in the form of a transesophageal pill endoscope on a string.
  • a pulsed laser e.g., a nanosecond Nd:YAG pumped OPO laser, tunable from 650-2500 nm, although other wavelengths are conceivable and are within the scope of the present disclosure
  • a pulsed laser e.g., a nanosecond Nd:YAG pumped OPO laser, tunable from 650-2500 nm, although other wavelengths are conceivable and are within the scope of the present disclosure
  • a pulsed laser e.g., a nanosecond Nd:YAG pumped OPO laser, tunable from 650-2500 nm, although other wavelengths are conceivable and are within the scope of the present disclosure
  • a pill arrangement 601 can be delivered to a pill arrangement 601 through a fused silica multimode optical fiber
  • a generated acoustic wave can be converted by an ultrasonic transducer 604 into an electric signal, which can be carried by an electric wire 605 to external devices.
  • the signal may be amplified, digitized, and acquired using the ultrasonic transducer 604 to a computer that can further analyze the signal to provide at least one characteristic of the tissue.
  • the exemplary pill arrangement 601 can be steered by an attached string 606 to come to a close contact with an esophageal wall to provide an appropriate acoustic coupling, and achieve a desirable view of the tissue.
  • FIG. 6( b ) illustrates another exemplary photoacoustic arrangement in the form of a wireless transesophageal pill endoscope according to a further exemplary embodiment of the present disclosure.
  • a miniature light source 612 e.g., a microchip laser, a pulsed laser diode, a modulated continuous-wave laser diode or a fiber laser
  • a battery or a remote power unit powered by a battery or a remote power unit
  • an ultrasonic transducer 613 can be provided which can detect a resultant acoustic wave, and transmit it to an external receiver.
  • the signal can then be acquired to a computer, and analyzed to provide information about the tissue.
  • the pill arrangement 611 can include a balloon 614 , which can be inflated with an acoustic coupling medium (e.g., water) to stop at one or more particular positions to detect, review or look at the tissue of interest.
  • An ultrasonic transducer is a device that can sense an acoustic wave. This device can be a piezoelectric transducer, a polyvinylidene fluoride film transducer, a capacitor micro-machined transducer and/or any acoustic sensor based on an optical interferometer.
  • the transducer can also include a single-element acoustic hydrophone or microphone, or an array of acoustic transducers.
  • the ultrasonic detection array can have different configurations, including, but are not limited to, a linear array parallel to the short- or long-axis of the pill 621 (mono-plane, as shown in FIG. 6( c )), a cross-patterned array 631 (bi-plane, as shown in FIG. 6( d )), a linear array which can be rotated in an arrangement 641 (multi-plane, as shown in FIG. 6( e )), a matrix array 651 (2-dimensional, as shown in FIG. 6( f )), or along a ring surrounding the pill arrangement 661 (as shown in FIG. 6( g )).
  • the ultrasonic array can be further curved in any direction to provide a geometric focusing.
  • an ultrasonic transducer can have a central frequency at, e.g., about 1-30 MHz.
  • the exemplary arrangement of other embodiments of the present disclosure can include a fluorescence imaging set-up configuration.
  • an exogenous or endogenous fluorophore in a tissue can be excited by a light at a wavelength ⁇ 1 , and can emit a second light at a red-shifted wavelength ⁇ 2 .
  • Exemplary fluorophore can be selectively detected by selecting a proper combination of excitation and emission spectral bands.
  • the fluorescence signals can be emitted from vulnerable plaque, including the NIR region of the electromagnetic spectrum, which corresponds to emission from lipid oxidative byproducts. The intensity of the emission can also be a quantitative measure of the concentration of the fluorophore.
  • a light source 702 e.g., a laser diode
  • a detector 703 e.g., a photodiode
  • a spectral filter 704 can be used to block unwanted light from reaching the detector 703 .
  • a balloon 705 can be attached to the pill endoscope arrangement 701 , and can be inflated to anchor the arrangement 701 to one or more particular location to measure a tissue of interest.
  • the fluorescence signal can be measured through a plurality of source-detector pairs, to provide a depth-resolved distribution of a fluorophore of interest using a reconstruction procedure (which is known to those having ordinary skill in the art) based on a light-tissue interaction model. It should be understood that other procedures and/or models that are known to those having ordinary skill in the art can be used with this exemplary embodiment, as well as with other exemplary embodiments that are described herein.
  • the exemplary arrangement can be configured to have an optical spectroscopy set-up configuration.
  • specific constituents of a tissue can have distinct optical spectra. It is possible to characterize the composition of the tissue, e.g., through a measurement of its optical spectra by decomposing the contributions from each constituent.
  • An exemplary optical spectroscopy arrangement according to an exemplary embodiment of the present disclosure is illustrated in FIG. 8 .
  • a light source 802 e.g., a superluminescent diode
  • a spectrometer 803 can be attached to the pill endoscope 801 , and can be inflated to anchor such exemplary pill endoscope arrangement 801 to one or more particular locations to measure the tissue of interest.
  • the optical spectra of the tissue as shown in FIG. 8 , can be obtained by taking the ratio between the spectra of the excitation light and the emission light.
  • a decomposing procedure may be used to estimate the concentration of a constituent of the tissue. It should be understood that other procedures and/or models that are known to those having ordinary skill in the art can be used with this exemplary embodiment, as well as with other exemplary embodiments that are described herein.
  • the exemplary arrangement/apparatus/endoscope can be provided in a laser speckle imaging set-up configuration.
  • the tissue is illuminated by a coherent light
  • a light scattered from the tissue can acquired by a camera showing a speckle pattern due to the interference.
  • the spatial and/or temporal fluctuation (s) of the speckle can indicate the tissue perfusion and/or the mechanical properties of the tissue.
  • the decorrelation time constant of the speckle intensity can be an index of viscoelasticity of a tissue that can be used to assess the structure and composition of an atherosclerotic plaque. (See Nadkarni, S. K. et al., “Characterization of Atherosclerotic Plaques by Laser Speckle Imaging”, Circulation 112, 885-892 (2005)).
  • An exemplary laser speckle imaging arrangement can include a transesophageal pill arrangement/endoscope, as illustrated in FIG. 9 .
  • the exemplary pill arrangement 901 can include a miniaturized light source 902 (e.g., a microchip laser, or a laser diode) which can illuminate a tissue with a coherent optical wave, and an optical wave scattered by the tissue can be imaged by a camera 903 (e.g., a CCD or CMOS camera).
  • An in-pill power unit/arrangement can energize both the source 902 and the camera 903 .
  • a balloon 904 can be attached to the pill arrangement 901 , and can be inflated to anchor it to one or more particular locations, facilitating the ability by the camera 903 to obtain speckled images from the tissue of interest for a particular time period.
  • an excitation light in the red and/or the near-infrared spectral range e.g., 600-1100 nm
  • a spatial filter can be used to selectively detect light scattered from a deep tissue.
  • the exemplary arrangement/endoscope can be configured to have an optical tomography set-up configuration.
  • a plurality of optical sources and detectors can be provided, and a measurement of a diffused light reemitted from tissue can be performed following an optical illumination through, e.g., a plurality of source-detector pairs.
  • a reconstruction procedure based on a light-tissue interaction model can be employed to inverse the measurements so as to obtain optical properties of the tissue (e.g., an absorption coefficient, a reduced scattering coefficient, etc.), or a dynamic property of a tissue (e.g., blood flow).
  • optical properties of the tissue e.g., an absorption coefficient, a reduced scattering coefficient, etc.
  • a dynamic property of a tissue e.g., blood flow
  • a pill endoscope/arrangement 1001 can include a plurality of sources 1002 (e.g., laser diodes) and a plurality of detectors 1003 (e.g., photodiodes).
  • a balloon 1004 can be attached to the pill 1001 , and can be inflated to anchor it to one or more particular locations when measuring or analyzing the tissue of interest.
  • Another exemplary advantage for using the inflated balloon 1004 in a diffuse optical tomography apparatus can be that the balloon 1004 can impose well-defined boundary conditions to simplify the reconstruction.
  • Sources 1002 can emit light in a sequential order (e.g., one source fires at a time), and the detectors 1003 can measure the resultant diffused reemission.
  • the exemplary measurement can be transferred to an external computer, and reconstructed to obtain a property of the tissue.
  • an ultrasonic imaging arrangement can be provided as illustrated in FIG. 11 .
  • a wireless pill endoscope 1101 can be provided that is sized to fit in an esophagus, and the pill endoscope 1101 can include an ultrasonic transducer 1102 that can emit a high-frequency acoustic wave to insonify a tissue of a heart or a blood vessel, and detect a resultant acoustic echo scattered from the tissue. Due to the preference to penetrate an esophageal wall, the ultrasonic transducer 1102 can have a central frequency, e.g., between about 1 and 30 MHz.
  • the detected acoustic signal can then be transferred to an external receiver, provided to a computer and analyzed to provide information about the tissue.
  • the pill endoscope 1101 can include a balloon 1103 , which can be inflated with an acoustic coupling medium (e.g., water) to stop at one or more particular positions to measure the tissue of interest.
  • the exemplary ultrasonic transducer 1102 of the exemplary endoscope/apparatus 1101 can be used (e.g., with a computer commented thereto) the map an anatomy of the tissue based on their acoustic reflectivity, and can locate an atherosclerotic plaque by detect the thickening of a blood vessel wall.
  • the exemplary ultrasonic set-up configuration shown in FIG. 11 can measure the blood flow based on the Doppler principle. For example, by measuring a dimension of a heart or the blood vessel, and the blood velocity therein, the exemplary apparatus can further quantify a cardiac output or a cardiac index. Additionally, by detecting a deformation of the tissue after exerting a known pressure on it, a mechanic property of the tissue can be obtained.
  • a combination of two or more exemplary embodiments according to the present disclosure can provide complementary information about a cardiovascular disease or function, and is still inside the scope of the present disclosure.
  • the ultrasonic transducer 604 can be configured to emit an acoustic wave, detect the resultant acoustic echo and thus perform an additional ultrasonic imaging.
  • the exemplary photoacoustic methods/procedures can be effective in obtaining functional and molecular information of the tissue, such as the molecular composition of a tissue, blood oxygenation, and temperature, while ultrasonic arrangement is good at mapping the structure of a tissue and measuring a blood flow.
  • exemplary ultrasonic structural imaging procedure(s) to guide a placement of the photo-acoustic probe/endoscope/arrangement at one or more particular locations to measure a physiological function of the tissue of interest, obtain comprehensive information of an atherosclerotic plaque, obtain additional cardiac functional indicators, such an oxygen uptake by a lung, an oxygen delivery and consumption to different parts of the body, and/or assess to which extent a stenosis impedes oxygen delivery to the heart, etc.
  • An implementation of the exemplary embodiments of the methods and procedures according to the present disclosure discussed herein can increase the contrast of OCT and OFDI intracoronary images, thus possibly reducing the time and increasing the accuracy of interpreted images.
  • Enhanced contrast and identification of areas with lipid can facilitate a rapid comprehensive visualization, and a guidance of local therapy methods and/or assessment of appropriate treatment options.
  • This additional exemplary information on the tissue component, compound or chemical that is obtained by the disclosed method can be computed or determined using a processing apparatus (e.g., one or more computers), and displayed in real time in two dimensions or three dimensions to guide the exemplary diagnostic and/or therapeutic procedure.
  • any reference to optical spectroscopy can include diffuse optical tomography, optical coherence tomography, optical frequency domain imaging, and/or spectroscopic photoacoustics modalities.
  • the exemplary catheters and/or endoscopes can be provided in various other vessels or orifices to measure different anatomical structures in proximity of the exemplary arrangements and/or structures.
  • the exemplary catheter(s)/arrangement(s)/endoscope(s) can be placed in the esophagus, and provided to measure a nearby anatomical structure, including the heart.

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